inflammation Flashcards
What causes the fifth cardinal sign of inflammation?
loss of function is caused by pain or swelling
what are DAMPS?
(damage associated)
Intracellular proteins released when plasma membrane is injured in a cell
A signal that there is serious cell damage, triggering inflammation
recognized by PRR
important reiteration
PRR’s are nonspecific and part of innate immunity
what is extravasation:
roll and squeeze allowing cells/molecules to enter interstitial from capillaries at site of infection/damage
note:
inflammation osmosis video is goated
How do neutrophils work?
Eat as many pathogens as possible then commit apoptosis (and release cytokines)
What causes Angiogenesis and what is it?
growth factors released by macrophages at the site of inflammation
Formation of new temporary blood vessels, which leave once the wound is healed
severe damage is replaced by a fibrous scar, mild damage can fully repair
Define antigen:
has to be immunogenic (causing proliferation of immune cells)
has to be reactive (antibodies can be produced against it)
ex. you could have a self antigen in autoimmune diseases
Incomplete antigens (HAPTEN)
binds with something in the body to become an antigen (like poison ivy binding to protein in our skin)
what is the goal of inflammation?
Innate immunity:
-subdue any infection
-remove necrotic debris from original injury
-restore normal function if possible
Acute Inflammation (Big picture)
first response (hours to days)
Vascular changes: dilation and increased permeability
short lived cells (neutrophils)
potent short lived mediators
sets stage for chronic inflammation
neutrophils and short lived mediators (acute inflam)
Neutrophil is the major cell involved in acute inflammation
Body improves blood flow to provide more neutrophils and mediators to the area of injury
Die within 10 hours after leaving the blood stream
Short lived mediators can damage host tissue also
Chronic Inflam (big picture)
second response (days to weeks to months to years)
monocyte become macrophages that can live as long as the host
degrades debree
orchestrates healing vs scarring
side note:
only making cards on takeaways, see powerpoint for inclusive info
Notes on inflammation white board image
Smooth muscle around vessel will relax
Mediators: clotting factors, kininogens, complement
Mast cells live in the tissue and contain lots of granules: release histamine (main), leukotrienes, prostaglandins (anti-prostaglandin meds?antihistamines?)
-mast cells also start cascade of inflammation
Tissue damage leads to release of endotoxin which stimulates mast cell to degranulate, releasing chemotaxins (draw cells to the area)
also release of bradykinin which stimulates pain receptors (swelling also causes pressure on receptors –> pain)
Mast cell released histamine causes vasodilation of smooth muscle surrounding area of interest, leading to increased blood flow + redness and warmth
also causes increased permeability of capillaries
Selectins are like nets waiting inside the capillaries to catch neutrophils/monocytes/MACROPHAGES and bring them to their target location
(antihistamine prevents edema??? Look it up, would it be used in someone with chronic inflammation?)
Macrophages release interleukins and tissue necrosis factors, which cause: 1-4 on white board image
2: lymph system transports factors vascular system hypothalamus, which releases PGE 2: causing fever (kills bacteria, increased metabolism and healing)
too much fever kills host cells, but it’s ok to leave low grade fevers because they are killing bacteria, not yet host cells
3: liver CRP (C reactive protein): very good blood test for acute inflammation
This process works for damage to the endothelium (trauma) and bacteria (not the same for viruses)
What is the purpose of endothelial cell contraction?
increase vascular permeability
direct endothelial injury
early (necrosis)
late (apoptosis)
leukocyte-mediated damage
later (hours)
ROS, prostaglandins, enyzmes
Not all vascular leakiness is created equal
hydrostatic pressure must be high and oncotic pressure low (low protein synthesis, high protein loss) to force molecules into interstitial spaces
Inflammation leakiness: increased endothelial permeability, endothelial damage, vasodilation and stasis
Exudate from inflammation
Protein-rich fluid plus cells (because leakiness is not due to low oncotic pressure aka lack of proteins)
Cellular response for acute inflammation:
neutrophil recruitment
phagocytosis and killing
mediator release (ROS, proteases, eicosanoids)
Acute Inflammation Triggers
Necrotic debris
infections
denatured protein
thrombus
uric acid (breakdown of DNA)
ATP (important and shouldn’t be floating around)
Arachidonic acid metabolites:
Prostaglandins
Leukotrienes
lipoxins
Defects in Acute Inflammation:
Unchecked inflammation with tissue injury
abscess formation
loss of function (pneumonia)
systemic effects (sepsis)
-hypotension (due to vasodilation)
-thrombosis
Chronic inflammation
an outcome of acute inflammation, causes minimal tissue injury and tissue can regenerate
-can lead to scarring
-can lead to resolution (neutralize mediator, normalize vessels, lymphatic drainage, macrophage cleanup)
Regeneration of a scar depends on:
-nature of injury
-intensity of injury
-host responses (large response leaves more exudate in tissues)
-cell and tissue type (ex. heart can’t regenerate)
-matrix integrity
-stem cells available
what is granulation tissue?
Scab
shows up after chronic inflammation with macrophages, followed by scar
Inflammation followed by Regeneration
Chronic inflammation if followed by regeneration, no granulation tissue or scarring
chronic inflammation and repair
moderate acute inflammation, recruit macrophages, angiogenesis, remodel matrix, complications of healing
Going from acute to chronic inflammation
Monocytes migrate to tissues and become macrophages, which then engulf debris from neutrophil apoptosis and necrotic tissue
fluid and proteins are picked up by lymphatic system and put back into circulation
macrophages release growth factors stimulating fibroblasts to repair/create new blood vessels
some macrophages then leave by blood or lymph (some stay for next injury)
“the macrophage is the key cell for driving repair and scarring” !!!!
What can cause chronic inflammation?
-Persistent injury (trauma, infection, necrosis)
-viral infection (neutrophils are no use intracellularly, so only recruit chronic inflammation cells like macrophages)
-autoimmune disorders (chronic response only)
Mononuclear cell inflammation
lymphocytes and macrophages (macrophages release lots of mediators that cause nonspecific damage)
prolonged duration (weeks to years) and ongoing tissue injury
repair:
angiogenesis
matrix deposition
Macrophages:
cytokines and chemokines
complement and coagulation factors
proteases, oxygen metabolites, elcosanolds (prostaglandins, thromboxanes, leukotrienes)
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